Interspecies Organogenesis for Human Transplantation

Author:

Crane Andrew T.1,Aravalli Rajagopal N.2,Asakura Atsushi34,Grande Andrew W.1,Krishna Venkatramana D.5,Carlson Daniel F.6,Cheeran Maxim C.-J.5ORCID,Danczyk Georgette1,Dutton James R.37,Hackett Perry B.7,Hu Wei-Shou8,Li Ling9,Lu Wei-Cheng1,Miller Zachary D.1ORCID,O’Brien Timothy D.35,Panoskaltsis-Mortari Angela10,Parr Ann M.13,Pearce Clairice1,Ruiz-Estevez Mercedes1,Shiao Maple1,Sipe Christopher J.1,Toman Nikolas G.1,Voth Joseph1,Xie Hui1,Steer Clifford J.3711,Low Walter C.13

Affiliation:

1. Department of Neurosurgery, University of Minnesota, Minneapolis, USA

2. Department of Electrical and Computer Engineering, University of Minnesota, Minneapolis, USA

3. Stem Cell Institute, University of Minnesota, Minneapolis, USA

4. Department of Neurology, University of Minnesota, Minneapolis, USA

5. Department of Veterinary Population Medicine, University of Minnesota, St. Paul, USA

6. Recombinetics, Inc., St. Paul, USA

7. Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, USA

8. Department of Chemical Engineering and Material Science, University of Minnesota, Minneapolis, USA

9. Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, USA

10. Department of Pediatrics, University of Minnesota, Minneapolis, USA

11. Department of Medicine, University of Minnesota, Minneapolis, USA

Abstract

Blastocyst complementation combined with gene editing is an emerging approach in the field of regenerative medicine that could potentially solve the worldwide problem of organ shortages for transplantation. In theory, blastocyst complementation can generate fully functional human organs or tissues, grown within genetically engineered livestock animals. Targeted deletion of a specific gene(s) using gene editing to cause deficiencies in organ development can open a niche for human stem cells to occupy, thus generating human tissues. Within this review, we will focus on the pancreas, liver, heart, kidney, lung, and skeletal muscle, as well as cells of the immune and nervous systems. Within each of these organ systems, we identify and discuss (i) the common causes of organ failure; (ii) the current state of regenerative therapies; and (iii) the candidate genes to knockout and enable specific exogenous organ development via the use of blastocyst complementation. We also highlight some of the current barriers limiting the success of blastocyst complementation.

Publisher

SAGE Publications

Subject

Transplantation,Cell Biology,Biomedical Engineering

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